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The Nature of Disease
Pathology for the Health Professions
Thomas H. McConnell
Chapter 4
Infectious Health Problems
1
Overview of Today’s Lecture
• Factors in Infection
• Overview of the classes of microorganisms
• Infection and Injury
– Classes of Microorganisms
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Bacteria
Viruses
Rickettsiae, Mycoplasma, Chlamydia
Fungi
Parasites
– Communicable Disease
– Clinical Manifestations
– Antimicrobial Therapy
• Immunodeficiency
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Review: Innate Antimicrobial Protection
From: Pathophysiology: A Clinical
Approach, Braun & Anderson,
Lippincott, 2011
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Introduction to Infectious Disease
• Infectious disease
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Transmissible (infectious) agent (microbes)
Invades through physical barriers (innate defenses)
Overcomes innate and adaptive immune defenses of host
Causes injury and disease (now called a pathogen)
• Endemic rate – normal expected rate of infection
• Epidemic – greater than normal infection rate
• Commensal relationship – organism benefits, we are not harmed
• Parasites – organisms that need the host to survive
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Microorganism and Human Relationship
• Mutual relationship
– Normal flora
– Relationship can be breached by injury
• Leave their normal sites and cause infection elsewhere
• Opportunistic microorganisms
– Normally held in check by immune system/defenses
– Do not usually cause disease except when a
person’s decreased immunity/defenses allow it
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Classes of Microorganisms
• Classes of Microorganisms (approx. from smallest to
largest)
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Prions (mis-folded proteins, PrP)
Viruses
Chlamydia (pathogenic bacteria, especially common in STIs)
Rickettsia (non-motile, gram negative bacteria)
Mycoplasma (bacterial genus lacking a cell wall)
Bacteria
Fungi
Protozoa (unicellular,
eukaryotic, usually motile
organisms)
– Helminths (multicellular,
parasitic worms)
– Ectoparasites (multicellular,
insect-like, invade skin)
Figure from: McConnell, The Nature of Disease, 2 ed., Wolters Kluwer, 2014
nd
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Factors Influencing Pathogen’s Infectivity
• True pathogens can circumvent the body’s normal
defenses, depending on the following factors:
– Pathogenicity
• Ability of an agent to produce disease
• Success depends on communicability, infectivity, extent of tissue
damage, and virulence
• Immunogenicity
– Ability of pathogens to induce an immune response
• Infectivity
– Ability of pathogen to invade and multiply in the host
– Involves attachment to cell surface, release of enzymes, escape from phagocytes,
spread through lymph and blood to tissues
• Virulence
– Capacity of a pathogen to cause severe disease; for example, measles virus
is of low virulence; while rabies virus is highly virulent
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Factors Influencing Infection (cont’d)
• Communicability
– Ability to spread from one individual to others and cause disease:
measles & pertussis spread very easily, HIV is of lower communicability
• Mechanism of action
– How the microorganism damages tissue
• Portal of entry
– Route by which a pathogenic microorganism infects the host
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Direct contact
Inhalation
Ingestion
Bites of an animal or insect
• Toxigenicity
– Ability to produce soluble toxins or endotoxins, factors that greatly
influence the pathogen’s degree of virulence
• Tropism – Preference for infect a particular tissue or cell
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Communicable Disease
• Communicable
Diseases are those
spread from person
to person
– Usually by infected
blood, body fluids
– All communicable
diseases are infectious
From: Pathophysiology: A Clinical Approach, Braun & Anderson, Lippincott, 2011
Chain of
Infection
• Modes of Transmission
(Mn: DIVIDE)
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Direct Contact
Ingestion
Vectors
Indirect Contact
Droplets (airborne)
Fomite -is any object or substance capable of carrying infectious
organisms and transferring them from one individual to another.
Skin cells, hair, clothing, and bedding are common hospital sources
of contamination.
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Host Reaction to Infectious Organisms
• Viruses
– Chronic inflammation
– Lymphocytes and monocytes
– Can be cytopathic or cytoproliferative
• Bacteria
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Suppurative (purulent) inflammation – acute
Neutrophil infilatrate at site and in blood (neutrophilia)
Exceptions: Chlamydia and Treponema pallidum (syphillis)
Exceptions: Mycobacterium tuberculosis -> granulomatous (chronic)
inflammation with lymphocytes and monocytes forming nodules
• Fungi
– Granulomatous inflammation
• Parasitic worms (helminths) – eosinophils
• Protozoa - Variable
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The Natural Course of Infection
(Resolution)
(Acute)
Figure from: McConnell, The Nature of Disease, 2nd ed., Wolters Kluwer, 2014
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Examples of Pathogen Defense Mechanisms
• Bacteria
– Produce surface coats that inhibit phagocytosis
• Outer coat gram+ org, waxy coat, LPS
– Produce toxins (leukocidins) that destroy neutrophils
– Molecules that destroy Ig’s: IgA proteases
• Viruses
– Many can mutate within cells where they are not available to
immune and inflammatory mechanisms
– Not available to antibodies in circulation
– Antigenic variations:
• Antigenic drift – mutation in key surface antigens
• Antigenic shifts – genetic recombination that changes antigenic
properties
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Viral Infections
• Characteristics of viruses:
– Dependent on host cells for
their replication
– No metabolism
– Simple organism
Figure from: Huether & McCance, Understanding Pathophysiology,
5th ed., Elsevier, 2012
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• Genetic material
• Surrounding layer of proteins (capsid)
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Usually a self-limiting infection
Spreads cell to cell
Virus then uncoats in cytoplasm
DNA virus replicates in nucleus (except poxviruses)
RNA virus replicates in cytoplasm (except influenza/retroviruses)
Post-infection immunity depends on whether or not virus mutates
regularly
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Acute (Transient) Viral Infections
• Respiratory-tropic
– Rhinoviruses (100 varieties); common cold
• Usually spread by person-to-person contact
• Respiratory droplet(airborne) transmission is possible
– Adenoviruses; Tonsilitis, conjunctivitis, bronchiolitis
– Respiratory Syncytial Virus (RSV)
• Major cause of lower respiratory tract infection in children
• Bronchiolitis, pneumonia
– Influenza (influenza viruses type A and B)
• Flu-like symptoms (fever, chills, nasal congestion, cough, myalgia, malaise)
• Spread mainly by respiratory droplets
• May cause problems in ‘at-risk’ segments of the population
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Acute (Transient) Viral Infections
• Gastrointestinal-tropic (usually fecal contamination)
– Rotavirus
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Most common cause of severe diarrhea in infants and young children
Fecal-Oral route transmission
Vomiting, severe diarrhea, dehydration
Common in daycare centers
– Norovirus (Norwalk virus)
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90% of non-bacterial gastroenteritis in older children and adults
Caused by fecally contaminated food, water
Transmission by person-to-person contact or aerosolization
Prevanlent in ‘close’ quarters: Cruise ships, long-term care facilities, overnight
camps, hospitals, prisons, dormatories
• Nausea, abdominal pain, vomiting, watery diarrhea
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Acute (Transient) Viral Infections
• Other transient viral infections
– Measles (rubeola)
• Highly contagious; nasal and oral secretions
• Characteristic maculopapular rash (flat, red area on skin covered with small confluent
bumps
• Rash-like Koplick spots on cheek mucosa
– Mumps
• Contagious (but less than measles)
• Tropic for salivary glands, esp. parotid
– Rubella (German measles)
• Contagious (but less than measles); droplet
• May be asymptomatic or brief, mild febrile illness
– Coxsackie (Types A and B)
• Type A is tropic for oral mucosa and skin
(hand-foot-and-mouth disease) ; usually infants/children
• Type B is tropic for heart, lung, pancreas, and
nervous system
• No vaccine
– Hepatitis A(HAV) – epidemic, fecal-oral transmission
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Persistent (Chronic) Viral Infections
• Immune system does not eliminate virus
– Latent – recurrent flare-ups
– Productive – chronic inflammation and tissue injury
– Transformative – transformation of normal tissue into neoplasm
• Latent
– Herpes simplex virus (HSV)
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type 1 (mainly oral cold sores) and type 2 (mainly genital)
Small, painful blisters in skin or mucosa
Tropic for sensory axons; then travels to neuron cell body
No vaccine (acyclovir can limit and lessen symptoms)
– Herpes zoster (varicella-zoster) virus – related to HSV (above)
• Acute infection is chickenpox (children typically)
• Usually mild, short-tem constitutional symptoms except in immuncompromised
• Tropic for neurons, persists, and may reactivate to cause shingles (adults)
– Cytomegalovirus (variant of herpesvirus)
• Tropic for blood monocytes; asymptomatic or may mimic infectious mononucleosis
• Can cross the placenta, be transmitted to newborn through vaginal secretions or milk
• Most common opportunistic in AIDS patients
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Persistent (Chronic) Viral Infections
• Productive Virus Infections
– Hepatitis B (HBV) (Ch. 12)
– Hepatitis C (HCV) (Ch. 12)
– Both: Chronic, productive scarring of liver (cirrhosis)
• Transformative Virus Infections
– Epstein-Barr Virus (EBV)
• Agent of infectious mononucleosis (IM), usually young adults
• Chronic infection linked to some lymphomas and carcinomas
– Human Papilloma Virus (HPV)
• Tropic for skin and squamous mucosa
• Some asymptomatic, some skin warts, anogential warts, cervical dysplasia/cancer
• Vaccine available for most types
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Bacteria
• Single-cell
• Single chromosome, no nucleus
(prokaryotic)
• Classified by
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Shape (cocci, bacilli, coccobacilli)
Requirement for oxygen
Gram stain (positive or negative)
Acid fast (mycobacterium, nocardia)
From: Pathophysiology: A Clinical Approach, Braun &
Anderson, Lippincott, 2011
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Bacteria
Figures from: Pathophysiology: A Clinical Approach, Braun & Anderson, Lippincott, 2011
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Bacterial Virulence & Toxins
• Bacterial toxin production
– Exotoxins
• Proteins and Enzymes released during growth
• Enzymatically inactivate or modify key cellular components
– Diptheria toxin; inhibits cellular protein synthesis
– Botulism toxin; decreases release of acetylcholine causing flaccid paralysis
– Tetanus toxin; decreases release of glycine/GABA causing spastic paralysis
• Immunogenic
– Antitoxin production
– Can produce antibodies against exotoxins
– Some vaccines available
– Endotoxins
– Lipopolysaccharides (LPS) contained in the cell walls of gram-negative
organisms released during cell destruction
– Pyrogenic (fever-producing) effects; endotoxic/septic shock
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Bacterial Virulence
• Bacteria in blood
– Presence = bacteremia
– Growth = septicemia (sepsis)
• failure of immune system to check bacterial growth
• Invasion of blood by bacteria
– A result of a failure of the body’s defense mechanisms
– By gram-negative bacteria
– Endotoxins released in the blood
• release of vasoactive peptides and cytokines
• produce widespread vasodilation leading to septic (endotoxic) shock
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Bacteria - Cocci
• Gram positive cocci
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Most are aerobic
Usually cause acute, intense, pyogenic infections
Staphylococci (grow in tight clusters), e.g., S. aureus
Streptococci (grow in twisted chains)
• Identified by
– Antigenic properties into groups ( A, B, D, etc.)
– Character of hemolysis they cause (green (α), clear (β), none)
• Examples:
– Streptococcus pneumoniae (pneumococcus) causes lobar pneumonia
– Streptococcus pyogenes
• Gram negative cocci
– Neisseria are only important ones; N. meningitidis
– Causes life-threatening meningitis, especially in children
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Streptococcal Diseases
Figure from: McConnell, The Nature of Disease, 2nd ed., Wolters Kluwer, 2014
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Bacteria - Bacilli
• Gram positive bacilli
– Illnesses caused are typically species-specific
– Examples:
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Corynebacterium Diptheriae (diptheria)
Listeria monocytogenes (food borne infections)
Bacillus anthracis (anthrax)
Clostridium (C. dificile, C. perfringens, C. tetani, C. botulinum)
• Gram negative bacilli
– Intestinal infections
• H. pylori, E. coli, Salmonella, Shigella, Vibrio cholera
– Respiratory infections
• H. influenza, Legionella pneumophilia, Bordatella pertussis,
Psuedomonas aeruginosa
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Rickettsiae, Mycoplasmas, and Spirochetes
• Have characteristics of both bacteria and viruses
• Rickettsiae
– Obligate intracellular parasites
– Also gram-negative bacteria
– Target human endothelium
• Mycoplasmas
– Lack cell wall
– Survive on surface of host cells
– Commonly found in human
urogenital & respiratory tracts
• Spirochetes
– Gram negative, flagellated, thin,
motile, corkscrew shaped
– Example: Borrelia Burgdorferi (Lyme disease)
Figures from: bioweb.uwlax.edu
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Mycobacteria Cause Chronic Infection
• Mycobacteria are aerobic, acid-fast, comma shaped
• M. tuberculosis, M. lepreae (leprosy), M. avium (common in
AIDS opportunistic infection), M. bovinum
• Mycobacterium Tuberculosis
– Tuberculosis (TB) is a major, chronic, progressive, and communicable
disease
– Lungs most commonly affected; vertebrae & meninges also
– Distinctive granulomatous inflammation
• Monocyte and lymphocyte infiltration
• Caseous necrosis with crumbly, cheese-like necrotic tissue
– Incidence has declined in US except in certain target
populations
• poor, crowded, debilitated, and aged at risk
• immunocompromised, DM, chronic lung diseases,
malnutrition, alcoholism
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Pathogenesis of Tuberculosis
Figure from: McConnell, The Nature of Disease, 2nd ed., Wolters Kluwer, 2014
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Pathology of Tuberculosis
• 10 TB
– Small focus of granulomatous inflammation
– Scarring causes calcified, necrotic lesions, Ghon tubercles, in lungs
(primary infection site)
– When Ghon tubercles also appear in hilar LN -> Ghon complex
• 10 progressive TB (only about 5% of clinical cases)
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Typically seen in children and target population
Bacterial spread is more extensive than primary TB
May ‘seed’ other organs through blood (miliary TB)
NO caseating granulomas (Why?)
• 20 TB (reactivation TB; about 95% of clinical cases)
– Characterized by caseating granulomatous inflammation since this
occurs in previously sensitized individuals
– Fewer granulomas, but they are typically larger
– Lesions typically seen in apex of lung
– May cavitate into airways and facilitate spread through coughing
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Diagnosis and Treatment of TB
• Typically mild clinical onset with fever, night sweats,
mild malaise, weight loss, and
poor appetite
– If neglected, causes wasting (‘consumption’)
– If progresses, productive cough perhaps with
blood
• Test is the Purified Protein Derivative
(PPD)
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Skin test for infection, not disease
After 2 weeks post infection, positive test
Almost all negative tests have not been infected
48-72 hours after PPD injection (on volar surface of forearm)
• Must be induration (hard, tense), not just erythematous, to be
positive
• 5-10 mm: high risk for development of active TB
• 10-15 mm: increased risk for development of active TB
• > 15 mm: unlikely to develop to active TB
From: Pinterest via
aplisolppd.com?
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Fungal Infection
• Characteristics of fungi
– Relatively large microorganisms
– Thick rigid cell walls without
peptidoglycans (resist penicillin
and cephalosporins)
– Eukaryotic (nucleated)
– Exist as
• single-celled yeasts; facultative
anaerobes
• multi-celled molds; aerobic
• Sometimes both (dimorphic fungi)
– Reproduce by simple division or budding
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Infection and Injury - Fungal Infection
• Pathogenicity
From: www.ringwormstreatment.com
– Adapt to host environment
• Wide temperature variations, digest keratin, low oxygen
– Suppress the immune defenses
– Usually controlled by phagocytes, T lymphocytes
• Diseases caused by fungi are called mycoses
– Superficial, deep, endemic (dimorphic fungi),
or opportunistic
• Fungi that invade the skin, hair, or nails are
known as dermatophytes (superficial mycoses)
– The diseases they produce are called tineas (ringworm)
• Tinea capitis, tinea pedis, and tinea cruris
• Deep fungal infections are life threatening and are commonly
opportunistic (e.g., with antibiotics or pH changes).
• *Changes that alter normal flora promote fungal infections
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Infection and Injury - Fungal Infection
• Candida albicans
– Usually superficial as commensals on skin and
mucous membranes
– Candidiasis or moniliasis
– Spread from superficial structures more serious
– Apergillus is another commensal that can become
dangerous in immunocomproised individuals
• Deep mycoses
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From: Pathophysiology: A Clinical Approach,
Braun & Anderson, Lippincott, 2011
B. dermatidis – Blastomycosis (endemic)
Coccidioids – Coccidiomycosis (SW US)
Histoplasma – Histoplasmosis (bat guano)
Pneumocystis jiroveci only occurs in immunocompromised
individuals
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Clinical Models – Tinea (Fungus)
• Group of fungal skin diseases that occur in several locations
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Feet (tinea pedis)
Nails (tinea unguium)
Scalp (tinea capitis)
Groin (tinea cruris)
Skin (tinea corporis/ringworm, tinea versicolor)
• Pathophysiology
– Major route of transmission is by direct contact with infected reservoir
– Some predisposing factors
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Exposure to moist conditions
Genetic predisposition
Immunocompromise
Sharing of hygiene facilities with infected individuals
– Fungus (dermatophyte) attaches to keratinized cells and causes thickening
– May be complicated by bacterial superinfection or invasive dermatophyte
invasion
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Infection and Injury - Parasitic Infection
• Parasite – organism that benefits at host’s expense
• Major classes of parasites
– Unicellular, nucleated, motile protozoa
• include malaria, amoebae, flagellates
• Cases of Primary Amoebic Meningoencephalitis in 2013 caused by
Naegleria fowleri
– Large worms (helminths)
• Flatworms (flukes), roundworms (nematodes), tapeworms (cestodes)
– Ectoparasites – life on surface of host: lice, scabies,
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More common in developing countries
Spread human to human via vectors
Usually ingested
Tissue damage
– May be direct or secondary to infestation itself with toxin damage
– May be from consequences of inflammatory/immune response
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Protozoa
– Malaria (Plasmodium spp.; most common protozoan infection worldwide)
• Vector is mosquito
• Invade/destroy RBCs
– Leishmaniasis (Leishmania spp.)
Insect vectors;
Infect blood
(2nd part of alphabet)
• Chronic, inflammatory disease
• Infects WBC; skin, mucous membranes, viscera
• Vectors are sandflies
– Trypanosomiasis (Trypanosoma spp.)
• Infects blood
• Vectors are several types of insects
• African sleeping sickness; Chagas disease (cats are reservoir)
– Amebiasis (Entameoba histolytica)
• Consumption of fecally contaminated food
• Intestine (diarrhea), portal blood to form amebic abscesses, brain and lung
Fecal contamination
Intestines; diarrhea
(1st part of alphabet)
– Giardiasis (Giardia lamblia; most common protozoan infection in US)
• Ingesting fecally contaminated water or produce (chlorination not effective)
• Acute or chronic diarrhea when symptomatic
– Cryptosporidiosis (Cryptosporidium; also called microsporidiosis)
• In soil, food, water, fecally contaminated surfaces
• diarrhea in immunocompromised
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Helminths (worms)
• *Peripheral blood eosinophilia is a hallmark
• Roundworms (nematodes)
– Filariasis
• Vector is mosquito
• Infects Lymphatics and subcutaneous tissue
• Lymphedema, usually of scrotum and legs (elephantiasis)
– Intestinal roundworms (Usually tropical areas; oral-fecal contamination; intestine)
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Ascariasis (Ascaris spp.) – intestinal bleeding/obstruction, anemia (feed on blood),
Hookworms – intestinal bleeding, anemia
Pinworm – common pediatric infection in US; intestine, perianal area
Trichinosis – eating inadequately cooked pork; spread to muscle (pain, fever)
• Flatworms (flukes, trematodes)
– Infect blood vessels, GI tract, lungs, or liver
– Schistosomiasis – most common of all worm infections; snail vector
– Tapeworms (cestodes)
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3 stages: eggs, larvae, adult
Intestinal infection
Adults are named for their intermediate host, e.g., fish, beef, pork; larvae are in muscle
When intermediate host is eaten (undercooked), larvae develop
– Echinococcosis (hydatid disease)
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Sexually Transmitted Infections (STIs)
• Infections communicated by sexual contact
• Can be cause by any type of microorganism
– Viruses, e.g., genital and anorectal warts by HPV, genital herpes, HIV
– Bacteria, e.g., syphillis, gonorrhea, Chlamydia, Mycoplasma
– Parasites, e.g., trichomoniasis (amebic), scabies (skin mites), lice
(pediculosis)
• Some non-STI infections can be transmitted sexually, e.g., viral
hepatitis
• Problematic because many cases are asymptomatic and this
increases the risk of transmission
• Safe-sex practices can prevent STIs
• Chlamydia (C. trachomatis) is most common STI in the world
• Chlamydia and gonorrhea (N. gonorrhoeae) are the most
common causes of STI-related infertility
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Infection and Injury – Countermeasures; Antimicrobials
• Antimicrobials (antibiotics)
– Usually products of fungi or bacteria that inhibit growth of bacteria
– Bacteriocidal (kill) vs. bacteriostatic (inhibit growth)
– General mechanisms of most antibiotics
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Inhibit synthesis of cell wall and other proteins
Damage cytoplasmic membrane
Alter metabolism of nucleic acid, inhibition of DNA synthesis
Modify energy (folic acid) metabolism
• Antimicrobial resistance mechanisms
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Genetic mutations transmitted to other bacteria by plasmid exchange
Inactivation and/or breakdown of antibiotic
Multidrug transporters in bacterial cell membrane inhibit uptake
Multiple antibiotic-resistance bacteria (e.g., MRSA, VISA, VRSA, etc.)
• Major problem in hospitals
• Inadequate patient compliance with antibiotic regimen
• Overuse/over-prescribing of antibiotics by healthcare professionals
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Infection and Injury – Countermeasures; Vaccines
• Vaccines
– Biologic preparations of weakened or dead pathogens
• Stimulate cellular or humoral immunity against virus
• Live, attenuated strains; not enough virus to cause disease (except in
immunocompromised individuals)
• Heat killed virus; outer protein coat stays intact to promote immune response
– Recombinant viral protein
– Long lasting immunity (artificial, active)
• Primary response is short-lived;
• Booster increases secondary response
– CDCP schedules @ http://www.cdc.gov/vaccines/schedules/index.html
– Vaccines against bacterial exotoxins are called ‘toxoids’, e.g., DPT
– Reluctance to vaccinate
• Most objections are based on incomplete or incorrect information
• Complications are rare
• Removal of thimerosal (Hg containing) from most vaccines in 2001 has lessened the
risk and increased the favorable perception about vaccines
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